Childhood Vitamin D Status and Circulating Insulin-like Peptide 3 as a Marker of Leydig Cell Functional Capacity in Young Adulthood: Findings from the Avon Longitudinal Study of Parents and Children.

Background/Objectives: Circulating insulin-like peptide 3 (INSL3) is a constitutively secreted product of mature Leydig cells and is considered a stable biomarker of Leydig cell functional capacity, a key determinant of androgenic status across the male lifespan. Since the adult Leydig cell population is established during late childhood and puberty, nutritional and metabolic exposures during these periods may contribute to later variation in young adult INSL3. To investigate whether childhood and adolescent nutritional/metabolic markers, particularly vitamin D, fatty acids, amino acids, and dietary trace-element intake, are associated with circulating INSL3 concentrations in young adulthood. Methods: Data were analysed from the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based UK birth cohort. Nutritional and metabolic markers measured during childhood and adolescence included vitamin D, fatty acid-related traits, glutamine, leucine, dietary zinc intake, and dietary selenium intake. Associations with circulating INSL3 at 17 and 24 years were first explored using bivariate correlation analysis. Variables showing signals of interest were then examined in multiple linear regression models using log-transformed data and relevant covariates, including BMI at 8 years and log-transformed exact age at the age-24 clinic visit. Results: Among the variables examined, vitamin D at 9 years showed a small positive association with INSL3 at 24 years (r = 0.098, n = 735, p = 0.008), remaining below the corrected threshold after both Benjamini-Hochberg and Bonferroni correction (q = 0.032 and Bonferroni-adjusted p = 0.032). This relationship remained evident after adjustment for BMI at 8 years and after further adjustment for log-transformed exact age at the age-24 clinic visit. In these multivariable models, BMI at 8 years showed little evidence of association with INSL3 at 24 years, whereas log-transformed exact age at the age-24 clinic visit showed a negative association with INSL3. In contrast, no meaningful associations were observed for fatty-acid-related measures. Among amino acids and dietary trace-element measures, glutamine at 17 years showed a weak nominal positive association with INSL3 at 24 years, but this did not remain below the threshold after multiple-testing correction. Conclusions: Childhood vitamin D status, particularly at 9 years of age, may represent an early-life factor associated with variation in adult Leydig cell functional capacity. Fatty acid-related measures showed no clear associations, while glutamine yielded only a weak exploratory signal. These findings support the concept that the childhood metabolic environment may influence the developmental establishment of adult Leydig cell capacity.